Inhibiting misfolded protein propagation in neurodegenerative diseases

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Project Title: Inhibiting misfolded protein propagation in neurodegenerative diseases
Project Number: CORDIS-209883
Project web address: Follow on CORDIS
 
Project Description:
Assemblies of tau and α-synuclein were shown to spread along interconnected neuronal networks suggesting broadly relevant therapeutic directions for Alzheimer’s and Parkinson’s disease. This requires a pre-clinical stage of development that has yet to be met. The scale of neurodegenerative disease burden in Europe calls for an unprecedented research effort that can only be achieved through collaboration between leading European laboratories and the pharmaceutical industry. To meet this ambition the IMPRiND consortium will synergistically accelerate progress to map and target critical steps in the propagation, proteostatic response and protection against misfolded α-synuclein and tau. Specifically we aim to (1) identify disease-relevant assemblies, imprint their biological properties in vitro and generate homogeneous populations to assay and interfere with their pathogenic effects; (2) develop and miniaturise assays to monitor secretion, up-take, clearance and oligomerisation using bimolecular fluorescence complementation of oligomeric species or transfer of untagged assemblies to fluorescently labelled fibril-naïve cells and measure markers of early proteotoxicity that are suitable for live imaging high content screens; (3) perform genetic screens based on disease-relevant gene/protein networks and assess druggability of identified targets; (4) deliver robust validation assays for these molecular events in complex cellular systems with greater functional resemblance to the native milieu of the brain such as iPSC-based and organotypic cultures (5) standardise pathological readouts in animal models for in vivo validation of modifiers, correlate them with novel peripheral or in situ markers using microdialysis to accelerate the assessment of therapeutic interventions and relevance to humans, e.g. by transplantation of human iPSC neurons in animals. IMPRiND will construct this entire pipeline to examine the prion-like properties of α-synuclein and tau and test their tractability against disease progression.
 
Project Terms:
topic corda pharmacology and pharmacy pharmacology pharmacogenomics drug discovery and design drug therapy neurodegenerative disorders protein synthesis modification and turnover biochemistry and molecular biology molecular and cellular neuroscience dementia
Project Title: Inhibiting misfolded protein propagation in neurodegenerative diseases
Project Number: CORDIS-209883
Project web address: Follow on CORDIS
 
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Project Title: Inhibiting misfolded protein propagation in neurodegenerative diseases
Project Number: CORDIS-209883
Project web address: Follow on CORDIS
 
Project Title Organization FY Funding
Project Title: Inhibiting misfolded protein propagation in neurodegenerative diseases
Project Number: CORDIS-209883
Project web address: Follow on CORDIS
 
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Project Title: Inhibiting misfolded protein propagation in neurodegenerative diseases
Project Number: CORDIS-209883
Project web address: Follow on CORDIS
 
Title Year
Project Title: Inhibiting misfolded protein propagation in neurodegenerative diseases
Project Number: CORDIS-209883
Project web address: Follow on CORDIS
 
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